Mycobacterium abscessus Glycopeptidolipid Prevents Respiratory Epithelial TLR2 Signaling as Measured by HβD2 Gene Expression and IL-8 Release

Mycobacterium abscessus has emerged as an important cause of lung infection, particularly in patients with bronchiectasis. Innate immune responses must be highly effective at preventing infection with M. abscessus because it is a ubiquitous environmental saprophyte and normal hosts are not commonly infected. M. abscessus exists as either a glycopeptidolipid (GPL) expressing variant (smooth phenotype) in which GPL masks underlying bioactive cell wall lipids, or as a variant lacking GPL which is immunostimulatory and invasive in macrophage infection models. Respiratory epithelium has been increasingly recognized as playing an important role in the innate immune response to pulmonary pathogens. Respiratory epithelial cells express toll-like receptors (TLRs) which mediate the innate immune response to pulmonary pathogens. Both interleukin-8 (IL-8) and human β-defensin 2 (HβD2) are expressed by respiratory epithelial cells in response to toll-like receptor 2 (TLR2) receptor stimulation. In this study, we demonstrate that respiratory epithelial cells respond to M. abscessus variants lacking GPL with expression of IL-8 and HβD2. Furthermore, we demonstrate that this interaction is mediated through TLR2. Conversely, M. abscessus expressing GPL does not stimulate expression of IL-8 or HβD2 by respiratory epithelial cells which is consistent with “masking” of underlying bioactive cell wall lipids by GPL. Because GPL-expressing smooth variants are the predominant phenotype existing in the environment, this provides an explanation whereby initial M. abscessus colonization of abnormal lung airways escapes detection by the innate immune system

Differential Modulation of TNF-α–Induced Apoptosis by Neisseria meningitidis

Infections by Neisseria meningitidis show duality between frequent asymptomatic carriage and occasional life-threatening disease. Bacterial and host factors involved in this balance are not fully understood. Cytopathic effects and cell damage may prelude to pathogenesis of isolates belonging to hyper-invasive lineages. We aimed to analyze cell–bacteria interactions using both pathogenic and carriage meningococcal isolates. Several pathogenic isolates of the ST-11 clonal complex and carriage isolates were used to infect human epithelial cells. Cytopathic effect was determined and apoptosis was scored using several methods (FITC-Annexin V staining followed by FACS analysis, caspase assays and DNA fragmentation). Only pathogenic isolates were able to induce apoptosis in human epithelial cells, mainly by lipooligosaccharide (endotoxin). Bioactive TNF-α is only detected when cells were infected by pathogenic isolates. At the opposite, carriage isolates seem to provoke shedding of the TNF-α receptor I (TNF-RI) from the surface that protect cells from apoptosis by chelating TNF-α. Ability to induce apoptosis and inflammation may represent major traits in the pathogenesis of N. meningitidis. However, our data strongly suggest that carriage isolates of meningococci reduce inflammatory response and apoptosis induction, resulting in the protection of their ecological niche at the human nasopharynx

Ethics of Medical Assistance in Dying for Non-Terminal Illness: A Comparison of Mental and Physical Illness in Canada and Europe

L’aide médicale à mourir (AMM) devrait être légalisée au Canada à partir de mars 2024 pour les personnes dont la seule condition médicale sous-jacente est un trouble ou une maladie mentale (AMM MM-SCMS). Dans le cadre de l’élaboration de lignes directrices visant à assurer la sécurité et la cohérence de l’AMM MM-SCMS, il convient d’accorder une attention suffisante à l’interprétation de la terminologie ambiguë de la législation actuelle et de veiller à ce que ces interprétations soient fondées sur des principes éthiques acceptables.Medical assistance in dying (MAiD) is scheduled to be legalized in Canada as of March 2024 for individuals with mental disorder/illness as their sole underlying medical condition (MAiD MD-SUMC). As guidelines are being developed for the safe and consistent provision of MAiD MD-SUMC, sufficient consideration must be given to the interpretation of ambiguous terminology in current legislation, and to ensuring sound use of acceptable ethics principles in these interpretations

Appendiceal adenocarcinoma presenting as a bladder tumor

We present a case of an appendiceal adenocarcinoma that invaded the urinary bladder, which was preoperatively mistaken for urachal adenocarcinoma. The patient underwent open removal of the umbilicus, urachus, partial cystectomy and bilateral pelvic lymph node dissection. Intraoperatively the tumor was noted to involve the appendix, and so an appendectomy was also performed. The pathology showed an appendiceal adenocarcinoma invading the bladder wall. Urologists must have a high degree of suspicion for spread from a gastrointestinal primary when adenocarcinoma is found within the urinary bladder